Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

Background  

Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells.     

Muscle oxygen consumption,determined by NIRS,in relation to external force and EMG

Local oxygen consumption in a muscle (VO(2)) can be determined by near infrared spectroscopy (NIRS). In principle it should be possible to use this measure to validate musculoskeletal models. However, the relationship between VO(2) and external force, or between VO(2) and surface EMG, as a measure for muscle activity, is hardly known. The aim of this study was: (1) to evaluate the characteristics of the relationship between VO(2) and external moments and (2) to determine whether differences exist between the EMG-moment relationship and the VO(2)-moment relationship. Subjects (n=5) were asked to perform isometric contractions exerting combinations of elbow flexion and pro/supination moments at force levels up to 70% of their maximum. Simultaneous surface-EMG and NIRS measurements were performed on the m. biceps breve (BB) and the m. brachioradialis (BR). A linear relationship was found between EMG and VO(2). For the BB VO(2) and EMG were linearly related to both the flexion moment and the pro/supination moment. However, for the BR only a linear relationship with flexion moment was found. As expected, based on the findings above, the relationship between VO(2) and elbow flexion moment can be described by a linear equation, under the conditions of this study (isometric, and force levels up to 70%). These findings suggest that load sharing is independent of force level and that next to EMG, VO(2) can be used for the validation of musculoskeletal models.     

Nonuniform quadriceps O2 consumption revealed by near infrared multipoint measurements

Single location muscle monitoring does not reflect the heterogeneous activation of the muscle group(s) during a given exercise. Vastus lateralis and rectus femoris O2 consumption (VO2) was investigated, noninvasively, at rest and during maximal voluntary contractions (MVC) using a 12-channel near-infrared continuous wave spectroscopy (NIR(CWS)) system (0.1 s acquisition time). VO2 either at rest or during MVC was found to be nonuniform in the 11 out of 12 measurement sites over a surface of 8 x 8 cm2. As expected, VO2 during exercise was significantly higher than VO2 at rest (P < 0.01). However, at each muscle measurement site no difference was found between the mean values (n = 12) of VO2 measured during a 5-s intermittent MVC and the VO2 values measured during 30-s continuous MVC (P = 0.25). These results strengthen the role of NIR(CWS) as a powerful tool for investigating the spatial and temporal features of muscle oxygenation changes as well as muscle VO2.     

Changes in cerebral oxygenation and blood flow during LBNP in spinal cord-injured individuals.

Spinal cord-injured (SCI) individuals, having a sympathetic nervous system lesion, experience hypotension during sitting and standing. Surprisingly, they experience few syncopal events. This suggests adaptations in cerebrovascular regulation. Therefore, changes in systemic circulation, cerebral blood flow, and oxygenation in eight SCI individuals were compared with eight able-bodied (AB) individuals. Systemic circulation was manipulated by lower body negative pressure at several levels down to -60 mmHg. At each level, we measured steady-state blood pressure, changes in cerebral blood velocity with transcranial Doppler, and cerebral oxygenation using near-infrared spectroscopy. We found that mean arterial pressure decreased significantly in SCI but not in AB individuals, in accordance with the sympathetic impairment in the SCI group. Cerebral blood flow velocity decreased during orthostatic stress in both groups, but this decrease was significantly greater in SCI individuals. Cerebral oxygenation decreased in both groups, with a tendency to a greater decrease in SCI individuals. Thus present data do not support an advantageous mechanism during orthostatic stress in the cerebrovascular regulation of SCI individuals.     

Performance of near-infrared spectroscopy in measuring local O(2) consumption and blood flow in skeletal muscle.

The aim of this study was to investigate local muscle O(2) consumption (muscV(O(2))) and forearm blood flow (FBF) in resting and exercising muscle by use of near-infrared spectroscopy (NIRS) and to compare the results with the global muscV(O(2)) and FBF derived from the well-established Fick method and plethysmography. muscV(O(2)) was derived from 1) NIRS using venous occlusion, 2) NIRS using arterial occlusion, and 3) the Fick method [muscV(O(2(Fick)))]. FBF was derived from 1) NIRS and 2) strain-gauge plethysmography. Twenty-six healthy subjects were tested at rest and during sustained isometric handgrip exercise. Local variations were investigated with two independent and simultaneously operating NIRS systems at two different muscles and two measurement depths. muscV(O(2)) increased more than fivefold in the active flexor digitorum superficialis muscle, and it increased 1.6 times in the brachioradialis muscle. The average increase in muscV(O(2(Fick))) was twofold. FBF increased 1.4 times independent of the muscle or the method. It is concluded that NIRS is an appropriate tool to provide information about local muscV(O(2)) and local FBF because both place and depth of the NIRS measurements reveal local differences that are not detectable by the more established, but also more global, Fick method.     

Fairy, tadpole, and clam shrimps (Branchiopoda) in seasonally inundated clay pans in the western Mojave Desert and effect on primary producers

Background

Fairy shrimps (Anostraca), tadpole shrimps (Notostraca), clam shrimps (Spinicaudata), algae (primarily filamentous blue-green algae [cyanobacteria]), and suspended organic particulates are dominant food web components of the seasonally inundated pans and playas of the western Mojave Desert in California. We examined the extent to which these branchiopods controlled algal abundance and species composition in clay pans between Rosamond and Rogers Dry Lakes. We surveyed branchiopods during the wet season to estimate abundances and then conducted a laboratory microcosm experiment, in which dried sediment containing cysts and the overlying algal crust were inundated and cultured. Microcosm trials were run with and without shrimps; each type of trial was run for two lengths of time: 30 and 60 days. We estimated the effect of shrimps on algae by measuring chlorophyll content and the relative abundance of algal species.

Results

We found two species of fairy shrimps (Branchinecta mackini and B. gigas), one tadpole shrimp (Lepidurus lemmoni), and a clam shrimp (Cyzicus setosa) in our wet-season field survey. We collected Branchinecta lindahli in a pilot study, but not subsequently. The dominant taxa were C. setosa and B. mackini, but abundances and species composition varied greatly among playas. The same species found in field surveys also occurred in the microcosm experiment. There were no significant differences as a function of experimental treatments for either chlorophyll content or algal species composition (Microcoleus vaginatus dominated all treatments).

Conclusions

The results suggest that there was no direct effect of shrimps on algae. Although the pans harbored an apparently high abundance of branchiopods, these animals had little role in regulating primary producers in this environment.     

Muscle O(2) consumption by NIRS: a theoretical model.

In the past, the measurement of O(2) consumption ((2)) by the muscle could be carried out noninvasively by near-infrared spectroscopy from oxyhemoglobin and/or deoxyhemoglobin measurements only at rest or during steady isometric contractions. In the present study, a mathematical model is developed allowing calculation, together with steady-state levels of (2), of the kinetics of (2) readjustment in the muscle from the onset of ischemic but aerobic constant-load isotonic exercises. The model, which is based on the known sequence of exoergonic metabolic pathways involved in muscle energetics, allows simultaneous fitting of batched data obtained during exercises performed at different workloads. A Monte Carlo simulation has been carried out to test the quality of the model and to define the most appropriate experimental approach to obtain the best results. The use of a series of experimental protocols obtained at different levels of mechanical power, rather than repetitions of the same load, appears to be the most suitable procedure.